Gene and Protein Information
class A G protein-coupled receptor
Species	TM	AA	Chromosomal Location	Gene Symbol	Gene Name	Reference
Human	7	466	8p21.2	ADRA1A	adrenoceptor alpha 1A
Mouse	7	466	14 D1	Adra1a	adrenergic receptor, alpha 1a
Rat	7	466	15p12	Adra1a	adrenoceptor alpha 1A

Previous and Unofficial Names

α1c | α1a | ADRA1C | ADRA1L1 | adrenergic alpha 1c receptor | adrenergic receptor alpha 1c | alpha 1A-adrenoceptor | alpha 1A-adrenoreceptor | alpha 1C-adrenergic receptor | alpha-1A adrenergic receptor | adrenergic receptor, alpha 1a

Database Links
Specialist databases
GPCRdb	ada1a_human (Hs), ada1a_mouse (Mm), ada1a_rat (Rn)
Other databases
Alphafold	P35348 (Hs), P97718 (Mm), P43140 (Rn)
ChEMBL Target	CHEMBL229 (Hs), CHEMBL2822 (Mm), CHEMBL319 (Rn)
DrugBank Target	P35348 (Hs)
Ensembl Gene	ENSG00000120907 (Hs), ENSMUSG00000045875 (Mm), ENSRNOG00000009522 (Rn)
Entrez Gene	148 (Hs), 11549 (Mm), 29412 (Rn)
Human Protein Atlas	ENSG00000120907 (Hs)
KEGG Gene	hsa:148 (Hs), mmu:11549 (Mm), rno:29412 (Rn)
OMIM	104221 (Hs)
Pharos	P35348 (Hs)
RefSeq Nucleotide	NM_000680 (Hs), NM_013461 (Mm), NM_017191 (Rn)
RefSeq Protein	NP_000671 (Hs), NP_038489 (Mm), NP_058887 (Rn)
UniProtKB	P35348 (Hs), P97718 (Mm), P43140 (Rn)
Wikipedia	ADRA1A (Hs)

Natural/Endogenous Ligands
(-)-adrenaline
(-)-noradrenaline

Potency order of endogenous ligands (Human)

(-)-noradrenaline = (-)-adrenaline

Download all structure-activity data for this target as a CSV file

Agonists
Key to terms and symbols	View all chemical structures	Click column headers to sort
Ligand Sp. Action Value Parameter Reference oxymetazoline Hs Full agonist 7.2 – 8.2 pKi 23,32,52,93,101,115,122,129 ⤷ pKi 7.2 – 8.2 [23,32,52,93,101,115,122,129] dabuzalgron Hs Agonist 7.4 pKi 13 ⤷ pKi 7.4 [13] A61603 Hs Full agonist 6.8 – 7.5 pKi 23,32,35,65,101 ⤷ pKi 6.8 – 7.5 [23,32,35,65,101] naphazoline Hs Full agonist 6.5 pKi 101 ⤷ pKi 6.5 [101] cirazoline Hs Full agonist 6.2 – 6.7 pKi 32,101 ⤷ pKi 6.2 – 6.7 [32,101] NS-49 Hs Partial agonist 6.2 pKi 93 ⤷ pKi 6.2 [93] (-)-adrenaline Hs Full agonist 5.1 – 6.5 pKi 52,101,115,122 ⤷ pKi 5.1 – 6.5 [52,101,115,122] (-)-noradrenaline Hs Full agonist 4.8 – 6.4 pKi 23,32,52,101,115,122,129 ⤷ pKi 4.8 – 6.4 [23,32,52,101,115,122,129] phenylephrine Hs Full agonist 4.9 – 5.4 pKi 23,32,101,129 ⤷ pKi 4.9 – 5.4 [23,32,101,129] (+)-adrenaline Hs Full agonist 5.0 pKi 115 ⤷ pKi 5.0 [115] methoxamine Hs Full agonist 4.6 – 5.2 pKi 23,32,101,115,122,129 ⤷ pKi 4.6 – 5.2 [23,32,101,115,122,129] A61603 Hs Full agonist 7.5 – 10.3 pEC50 23,32,65,101 ⤷ pEC50 7.5 – 10.3 [23,32,65,101] oxymetazoline Hs Full agonist 7.2 – 9.3 pEC50 23,32,101 ⤷ pEC50 7.2 – 9.3 [23,32,101] cirazoline Hs Full agonist 6.9 – 9.2 pEC50 32,101 ⤷ pEC50 6.9 – 9.2 [32,101] naphazoline Hs Full agonist 6.6 – 8.9 pEC50 101 ⤷ pEC50 6.6 – 8.9 [101] (-)-adrenaline Hs Full agonist 5.6 – 9.1 pEC50 101 ⤷ pEC50 5.6 – 9.1 [101] (-)-noradrenaline Hs Full agonist 5.5 – 8.6 pEC50 23,32,101 ⤷ pEC50 5.5 – 8.6 [23,32,101] phenylephrine Hs Full agonist 4.9 – 8.3 pEC50 23,32,101 ⤷ pEC50 4.9 – 8.3 [23,32,101] methoxamine Hs Full agonist 4.4 – 8.1 pEC50 23,32,101 ⤷ pEC50 4.4 – 8.1 [23,32,101]
Agonist Comments
The first α1A-adrenoceptor to be cloned was the bovine homolog. No species significant differences in pharmacology have been identified. The approved drug oxymetazoline displays α1A-AR selectivity but profile is complicated by significant actions at α2-AR and 5HT1B receptors [23]. This does not preclude clinically relevant activity at other adrenoceptors. A61603 is highly selective for the α1A-AR [23,32,101]. Note that EC50 values have been determined in a variety of assay formats measuring intracellular Ca2+ release, ERK1/2 phosphorylation, extracellular acidification rate and cAMP accumulation. Clinical uses: adrenaline and noradrenaline are used as intravenous infusion for shock and likely act through both α and β-AR. Oxymetazoline and xylometazoline are used as nasal decongestants.

Antagonists
Key to terms and symbols	View all chemical structures	Click column headers to sort
Ligand Sp. Action Value Parameter Reference olanzapine Rn Antagonist 7.4 pA2 92 ⤷ pA2 7.4 [92] Description: Measured as antagonism of phenylephrine-induced contraction of endothelium-denuded rat small mesenteric artery. [125I]HEAT (BE2254) Hs Antagonist 9.7 – 9.9 pKd 80,93,122 ⤷ pKd 9.7 – 9.9 [80,93,122] [3H]prazosin Hs Inverse agonist 9.1 pKd 102 ⤷ pKd 9.1 [102] NAN 190 Hs Antagonist 10.1 pKi 147 ⤷ pKi 10.1 [147] tamsulosin Hs Antagonist 9.4 – 10.7 pKi 17,24,35,102,104,115,122,139 ⤷ pKi 9.4 – 10.7 [17,24,35,102,104,115,122,139] silodosin Hs Antagonist 9.6 – 10.4 pKi 102,104,122 ⤷ pKi 9.6 – 10.4 [102,104,122] WB 4101 Rn Antagonist 9.5 – 10.2 pKi 54,135 ⤷ pKi 9.5 – 10.2 [54,135] upidosin Hs Antagonist 9.6 pKi 35 ⤷ pKi 9.6 [35] RS-100329 Hs Antagonist 9.6 pKi 102,139 ⤷ pKi 9.6 [102,139] S(+)-niguldipine Hs Antagonist 9.1 – 10.0 pKi 35,102,122 ⤷ pKi 9.1 – 10.0 [35,102,122] prazosin Rn Inverse agonist 9.5 pKi 135 ⤷ pKi 9.5 [135] prazosin Hs Inverse agonist 9.0 – 9.9 pKi 17,24,35,102,122,139 ⤷ pKi 9.0 – 9.9 [17,24,35,102,122,139] WB 4101 Hs Antagonist 9.0 – 9.8 pKi 17,24,35,102,122 ⤷ pKi 9.0 – 9.8 [17,24,35,102,122] ρ-Da1a Hs Antagonist 9.2 – 9.5 pKi 80,106 ⤷ pKi 9.2 – 9.5 [80,106] S(+)-niguldipine Rn Antagonist 9.3 pKi 135 ⤷ pKi 9.3 [135] SNAP5089 Hs Antagonist 8.8 – 9.4 pKi 50,70,102,136 ⤷ pKi 8.8 – 9.4 [50,70,102,136] 5-methylurapidil Hs Antagonist 8.9 – 9.2 pKi 17,35,70,102,113,122,147 ⤷ pKi 8.9 – 9.2 [17,35,70,102,113,122,147] 5-methylurapidil Rn Antagonist 9.0 pKi 135 ⤷ pKi 9.0 [135] Ro-70-0004 Hs Antagonist 8.9 pKi 139 ⤷ pKi 8.9 [139] doxazosin Hs Antagonist 8.4 – 9.3 pKi 48,102,104 ⤷ pKi 8.4 – 9.3 (Ki 5.37x10-10 M) [48,102,104] RS-17053 Hs Antagonist 8.3 – 9.3 pKi 17,24,34-35,102 ⤷ pKi 8.3 – 9.3 [17,24,34-35,102] BODIPY FL-prazosin Hs Inverse agonist 8.7 pKi 83 ⤷ pKi 8.7 (Ki 2x10-9 M) [83] roxindole Hs Antagonist 8.6 pKi 86 ⤷ pKi 8.6 [86] HEAT (BE2254) Hs Antagonist 8.6 pKi 102 ⤷ pKi 8.6 [102] A-119637 Hs Antagonist 8.6 pKi 16 ⤷ pKi 8.6 [16] A-119637 Rn Antagonist 8.6 pKi 16 ⤷ pKi 8.6 [16] risperidone Hs Antagonist 8.4 – 8.7 pKi 102,147 ⤷ pKi 8.4 – 8.7 [102,147] terguride Hs Antagonist 8.5 pKi 86 ⤷ pKi 8.5 [86] A-123189 Rn Antagonist 8.5 pKi 16 ⤷ pKi 8.5 [16] ritanserin Hs Antagonist 8.4 pKi 147 ⤷ pKi 8.4 [147] (+)-cyclazosin Hs Antagonist 7.9 – 8.9 pKi 39,102 ⤷ pKi 7.9 – 8.9 [39,102] A-123189 Hs Antagonist 8.4 pKi 16 ⤷ pKi 8.4 [16] indoramin Hs Antagonist 8.4 pKi 24,35,102 ⤷ pKi 8.4 [24,35,102] phentolamine Hs Antagonist 8.2 – 8.6 pKi 102,122 ⤷ pKi 8.2 – 8.6 [102,122] carvedilol Hs Antagonist 8.4 pKi 102 ⤷ pKi 8.4 [102] spiperone Hs Antagonist 8.3 pKi 147 ⤷ pKi 8.3 [147] terazosin Hs Antagonist 7.9 – 8.7 pKi 84,102,104 ⤷ pKi 7.9 – 8.7 (Ki 2x10-9 M) [84,102,104] clozapine Hs Antagonist 8.1 – 8.3 pKi 102,147 ⤷ pKi 8.1 – 8.3 [102,147] ketanserin Hs Antagonist 8.2 pKi 147 ⤷ pKi 8.2 [147] amitriptyline Hs Antagonist 8.2 pKi 102 ⤷ pKi 8.2 [102] nortriptyline Hs Antagonist 8.2 pKi 102 ⤷ pKi 8.2 [102] lisuride Hs Antagonist 7.9 – 8.3 pKi 86,102 ⤷ pKi 7.9 – 8.3 [86,102] phentolamine Rn Antagonist 8.1 pKi 135 ⤷ pKi 8.1 [135] clomipramine Hs Antagonist 8.1 pKi 102 ⤷ pKi 8.1 [102] alfuzosin Hs Antagonist 7.8 – 8.1 pKi 50,102,104 ⤷ pKi 7.8 – 8.1 (Ki 8.2x10-9 M) [50,102,104] KMUP-1 Rn Antagonist 7.7 pKi 76 ⤷ pKi 7.7 [76] mianserin Hs Antagonist 7.6 pKi 147 ⤷ pKi 7.6 [147] cyproheptadine Hs Antagonist 7.4 pKi 147 ⤷ pKi 7.4 [147] labetalol Hs Antagonist 7.3 pKi 101 ⤷ pKi 7.3 [101] spiroxatrine Hs Antagonist 6.9 – 7.3 pKi 102,147 ⤷ pKi 6.9 – 7.3 [102,147] BMY-7378 Rn Antagonist 7.0 pKi 16 ⤷ pKi 7.0 [16] BMY-7378 Hs Antagonist 6.6 – 7.0 pKi 16,102,147 ⤷ pKi 6.6 – 7.0 [16,102,147] cabergoline Hs Antagonist 6.5 pKi 86 ⤷ pKi 6.5 [86] piribedil Hs Antagonist 6.1 pKi 86 ⤷ pKi 6.1 [86] MT-1207 Hs Antagonist >10.0 pIC50 133 ⤷ pIC50 >10.0 (IC50 <1x10-10 M) [133] labetalol Hs Antagonist 7.5 – 7.9 pIC50 101 ⤷ pIC50 7.5 – 7.9 [101]
View species-specific antagonist tables
Antagonist Comments
Compounds such as prazosin and RS-17053 show unexpectedly low potency in certain isolated tissue assays [34-35]. This was postulated to result from a novel α1- adrenoceptor subtype (α1L), but is now thought to result from differences in α1A-AR characteristics dependent on the tissue or assay environment [42,137]. Silodosin, niguldipine, SNAP5089, RS-100329 and Ro-70-0004 are selective for α1A-ARs over the α1B- and α1D-AR subtypes [102,139]. The insurmountable antagonist ρ-Da1a is also α1A-AR subtype selective. Some antidepressants such as amitriptyline and clomipramine are selective for α1A-AR vs. other α1-AR subtypes [102]. BMY-7378 is a partial agonist in some systems [101]. Phenoxybenzamine is an irreversible α1-AR antagonist used to block the pressor effects of catecholamines prior to surgery for phaeochromocytoma. Doxazosin, alfuzosin, prazosin, tamsulosin, terazosin and cyclazosin are selective for α1-ARs vs. α2-ARs. Lisuride behaves as a partial agonist in some systems [101]. Compounds designated as "partial inverse agonists" [85] are listed as neutral antagonists. Bodipy FL-prazosin (QAPB) has been used to examine the cellular localisation of α1-adrenoceptors. Carvedilol is regarded as predominantly a β-AR antagonist, and it is this property that is primarily responsible for its usefulness in treating cardiac failure but it also potently inhibits α1-AR. It is somewhat selective for α1A-AR. Labetalol has similar properties but is less potent and is considered safe for use in pregnancy to treat eclampsia and pre-eclampsia. It also behaves as a partial agonist in some systems. Clinical uses: α1-AR antagonists are used to treat hypertension, benign prostatic hyperplasia, phaeochromocytoma and PTSD.

Allosteric Modulators
Key to terms and symbols		Click column headers to sort
Ligand Sp. Action Value Parameter Reference rho-TIA Rn Negative 5.0 pKi 116 ⤷ pKi 5.0 (Ki 1x10-5 M) [116]
Allosteric Modulator Comments
Whilst diazepam reduces the potency of phenylephrine to stimulate the inositol phosphate (IP) response in Rat-1 fibroblasts expressing the α1A-AR, no change in the maximum IP response is observed. In contrast, the maximum IP response to clonidine (a weak partial agonist at α1A-AR) is increased by diazepam, midazolam and lorazepam, suggesting that the ability to detect allosteric potentiation is a function of both the intrinsic activity of the α1-AR agonist and the activity of the proposed modulator [134]. Data published by Williams et al. (2018) show that diazepam is not a direct allosteric modulator of α1-adrenoceptors [138], but is able to modulate receptor activity via inhibition of phosphodiesterase 4. Amiloride analogues increase the dissociation rate of prazosin from the α1A-adrenoceptor [46]. Possible allosteric inhibition has been shown with ρ-TIA, a member of the ρ-conopeptide class of toxins derived from cone snails. ρ-TIA acts as an α1-adrenoceptor antagonist and is able to inhibit the norepinephrine-evoked increases in cytosolic-free calcium concentration and contractility. N-terminally truncated ρ-TIA analogues are less active than the full-length peptide. Upon deletion of the fourth residue of full-length ρ-TIA (in the form of the analogue TIA5-19), antagonist activity is observed at 65% compared to the response observed in full length ρ-TIA [116].

Primary Transduction Mechanisms
Transducer	Effector/Response
Gq/G11 family	Phospholipase C stimulation Calcium channel Other - See Comments
Comments:  The α1A-adrenoceptor is coupled to calcium release and inositol phosphate production (i.e. to Gq) more efficiently than the other α1-AR subtypes. The α1A-adrenoceptor is coupled to activation and translocation of Snapin and the TRPC6 channel to the plasma membrane and subsequent increase in Calcium entry and contractility.
References:  46,85

Secondary Transduction Mechanisms
Transducer	Effector/Response
G12/G13 family	Phospholipase A2 stimulation Phospholipase D stimulation Other - See Comments
Comments:  α1-adrenoceptors (all subtypes) can also activate protein kinase C, mitogen activated protein kinases. G13 coupling observed in transfected CHO cells to regulate arachidonic acid release. PKCzeta coupling to phospholipase D observed in transfected rat-1 fibroblasts. α1A- and α1B-adrenoceptors also couple to adenylyl cyclase to increase cAMP [23,101] but agonists have low potency.
References:  46,63,85,99

Tissue Distribution
Cauda epididymis. Species:  Human Technique:  RT-PCR, receptor binding, inhibition of contraction by selective antagonists. References:  96
In the human brain, the highest levels of α1A message are found in olfactory system, hypothalamic nuclei and in regions of the brainstem and spinal cord related to motor function. Also expressed in the hippocampus. Species:  Human Technique:  in situ hybridisation (including oligonucleotide labelling) References:  27,126
Dissociated, prostatic smooth muscle cells- plasmalemmal membrane and on intracellular compartments. Species:  Human Technique:  Confocal microscopy. References:  78
High expression levels of α1A-adrenoceptor mRNA are found in the heart, liver, cerebellum and cerebral cortex. Species:  Human Technique:  RNase protection assay References:  100
Prostate Species:  Human Technique:  Northern blot, RT PCR, receptor binding References:  33
Bladder and urethra. Species:  Human Technique:  RT PCR, receptor binding References:  123
Lymphocytes, saphenous vein. Species:  Human Technique:  in situ hybridisation References:  130,144
The α1A-adrenoceptor is the predominant subtype in human prostate and urethra. Species:  Human Technique:  Immunohistochemistry. References:  132
Bladder and urethra. Species:  Mouse Technique:  RT PCR, functional responses References:  6
Glucose uptake into fat, skeletal muscle and heart Species:  Mouse Technique:  KO mice and mice expressing a constitutively active α1A-adrenoceptor References:  121
Expressed in various neurons in the cerebral cortex, hippocampus, hypothalamus, midbrain, cerebellum, spinal cord; GABAergic interneurons and NG2 oligodendrocyte progenitors. Species:  Mouse Technique:  Systemic promoter-GFP transgenic model, RT PCR, receptor binding. References:  18,97
Epididymis. Species:  Rat Technique:  Radionucleotide binding, ribonuclease protection assay References:  105
Renal resistance arteries. Species:  Rat Technique:  Radioligand binding References:  110
Proximal and distal tail artery. Species:  Rat Technique:  RT-PCR and functional studies with selective agonists and antagonists References:  62
Prefrontal cortex. Species:  Rat Technique:  in situ hybridisation. References:  111
Taste buds, left ventricle, aorta, tail and mesenteric arteries. Species:  Rat Technique:  RT-PCR References:  10,79,151

Expression Datasets
Show »« Hide Log average relative transcript abundance in mouse tissues measured by qPCR from Regard, J.B., Sato, I.T., and Coughlin, S.R. (2008). Anatomical profiling of G protein-coupled receptor expression. Cell, 135(3): 561-71. [PMID:18984166] [Raw data: website] There should be a chart of expression data here, you may need to enable JavaScript!

Functional Assays
α1A-AR differentially couples to STAT3 phosphorylation through PKC epsilon and delta. Species:  Mouse Tissue:  Cardiomyocytes. Response measured:  Receptor coupling to STAT3, JAK2 and SRC. References:  119
Nuclear α1A-ARs activated ERK localized to caveolae at plasma membrane and receptor oligomerization. Species:  Mouse Tissue:  Cardiomyocytes. Response measured:  Nuclear localization/co-localization, ERK1/2 signaling. References:  141-142
RGS2 interacts with α1A-AR third intracellular loop to inhibit signal transduction. Species:  Human Tissue:  Transfected HEK 293 cells. Response measured:  Receptor/RGS2 association, IP3 accumulation, radioligand binding. References:  45
α1A-AR mediated p90 ribosomal S6 kinase activation increases early gene regulation. Species:  Rat Tissue:  Heart. Response measured:  Cardiomyocyte gene expression, pERK1/2, pRSK, cardiomyocyte transcriptome References:  9
Constitutive internalisation of the α1A-AR. Species:  Rat Tissue:  Transfected Rat-1 fibroblasts. Response measured:  Receptor traffiking with HA tagged α1A-AR/GFP fusion protein, IP3 accumulation. References:  90
α1A-AR coupling to G proteins is required for second messenger, mitogenic and transcriptional responses. Species:  Human Tissue:  Transfected PC12 cells. Response measured:  G-protein coupling: calcium and inositol phosphate responses, MAK kinase activity, tyrosine kinase Pyk2 activity and transcriptional responses. References:  69
α1A-AR regulates the secretion of extracellular matrix, cell adhesion and migration. Species:  Rat Tissue:  Rat-1 fibroblasts stably transfected with human α1A-AR. Response measured:  Secretion of hyaluronan, CD44, IL-6, syndecan-4, tenascin-C, increases in cell adhesion and inhibition of cell migration, microarray analysis, PCR. References:  117
Extracellular loop residues required for α1-AR subtype binding. Species:  Rat Tissue:  Transfected COS-1 cells. Response measured:  Radioligand binding: Q177G, I178V, N179T α1A-AR mutations decrease binding affinity for phentolamine and WB4101. References:  152
Role of serine interactions for α1A-AR binding and activation. Species:  Rat Tissue:  Transfected COS-1 cells. Response measured:  Radioligand binding, inositol phosphate production, site directed mutagenesis. References:  57
M292L mutation in the α1A-AR causes constitutive activity. Species:  Rat Tissue:  Transfected COS-1 cells. Response measured:  Phospholipase C and phospholipase A2 activity and agonist potency. References:  56
α1A-AR differentiates fibroblasts to smooth muscle, induces hypertrophy and cell cycle arrest and alters p27, p21, pRb, cyclin D1, cdk2 & 4, pcna. Species:  Rat Tissue:  Transfected rat-1 fibroblasts. Response measured:  Diffferentiation, hypertrophy and cell cycle arrest. References:  109
Androgen effects on α1A-AR subtypes in rat seminal vesicle contractile responses. Species:  Rat Tissue:  Seminal vesicles. Response measured:  mRNA by ribonuclease protection, contraction. References:  82
α1A-AR is the major subtype involved in norepinephrine-induced contraction of mouse ureter. Species:  Mouse Tissue:  Isolated ureteral preparations. Response measured:  mRNA expression, inhibition of norepinephrine mediated contractions by subtype selective α1-AR antagonists. References:  67
Activation of α1A-AR increases cardiomyocyte shortening and increases myofilament Ca2+ sensitivity which is potentiated by propofol. Species:  Rat Tissue:  Primary ventricular cardiomyocytes. Response measured:  Contraction, Ca2+ levels. References:  37
Role of α1A-AR in post infarct remodelling, dysfunction and survival. Species:  Mouse Tissue:  Heart muscle. Response measured:  Cardiac specific over expression of α1A-AR (rat), LV shortening, dP/dtmax References:  30
Isolated Vas deferens. Species:  Rat Tissue:  Prostatic and epididymal Vas deferens. Response measured:  Contraction, [3H]prazosin binding. References:  94
Pleiotropism of the α1A-AR Species:  Human Tissue:  Prostate Response measured:  Contraction, [3H]prozosin binding, IP3 accumulation. References:  35
Cell cycle arrest. Species:  Rat Tissue:  Transfected Rat-1 fibroblasts. Response measured:  Activities of CDK-6, cyclin E-associated kinase and cell cycle kinase inhibitor p27Kip1. References:  40
Heteromeric complex formation between atypical chemokine receptor 3 and α1A-AR. Species:  Human Tissue:  hVSMC, HEK293 or CHO cells Response measured:  Proximity ligation assay, BRET References:  5,31,38,91
Allosteric modulation of α1A-AR by 9-aminoacridine compounds. Species:  Human Tissue:  Transient transfection of COS1 cells. Response measured:  [3H]prazosin binding, IP3 accumulation References:  15
α1A-AR endocytic pathway involves ERK but not Gq/PLC/PKC signaling. Species:  Human Tissue:  Transfected HEK 293 cells. Response measured:  ERK 1/2 phosphorylation. References:  77
α1A-AR is a lipid raft protein and mediates signaling from rafts but exits rafts for internalization through clathrin-coated pits. Species:  Rat Tissue:  Rat-1 fibroblasts expressing α1A-AR. Response measured:  Fluorescence resonance energy transfer and confocal measurement of receptor distribution and internalization. References:  89
Biased agonism at α1A-AR. Species:  Human Tissue:  Stably transfected CHO-K1 cells Response measured:  Cell membrane [125I]HEAT binding, Ca2+ mobilisation, cAMP accumulation, ERK1/2 phosphorylation, ECAR. References:  23,32
Selectivity of α-adrenoceptor agonists for the human α1A, α1B- and α1D-adrenoceptors. Species:  Human Tissue:  Stably transfected CHO-K1 cells Response measured:  Whole cell [3H]prazosin binding, Ca2+ mobilisation, cAMP accumulation, ERK1/2 phosphorylation References:  101
The affinity and selectivity of α-adrenoceptor antagonists, antidepressants, and antipsychotics for the human α1A, α1B, and α1D-adrenoceptors Species:  Human Tissue:  Stably transfected CHO-K1 cells Response measured:  Whole cell [3H]prazosin binding References:  102
Determination of the functional α1A-AR phenotype mediating contraction of human contractile tissue. Species:  Human Tissue:  Erectile tissue, vas deferens. Response measured:  [3H]tamsulosin binding, inhibition of noradrenaline mediated contractions by subtype-selective antagonists. References:  25-26
Selective insurmountable antagonism of α1A-AR by green mamba venom ρ-Da1a. Species:  Human Tissue:  CHO-K1 cells stably expressing human α1A-AR. Response measured:  [3H]prazosin, [125I]HEAT binding, agonist stimulated Ca2+ mobilisation References:  80
Determinants of agonist binding to the α1A-AR. Species:  Rat Tissue:  Transiently transfected COS-1 cells. Response measured:  Radioligand binding, site directed mutagenesis. References:  55,81
Role of α1A-AR in cardiac contractility. Species:  Mouse Tissue:  Heart muscle. Response measured:  Contractile function, Ca2+ levels, Snapin, TRPC1, TRPC6 levels, cardiac specific over expression of α1A-AR (rat). References:  87
Anti-apoptotic and protective effects of α1A-AR in cardiac ischaemia. Species:  Mouse Tissue:  Cardiac myocytes and HL-1 cells Response measured:  [3H]deoxyglucose uptake, GLUT4 translocation References:  120

Physiological Functions
Contraction of stromal and capsular smooth muscle to control urethral resistance. Species:  Human Tissue:  Prostate. References:  51
Contraction of urethral smooth muscle. Species:  Human Tissue:  Urethra. References:  128
Contraction of skeletal muscle resistance arteries. Species:  Human Tissue:  Vasculature. References:  60
Glucose uptake in heart. Species:  Rat Tissue:  Cardiomyocyte References:  112
Orthostatic hypotensive effect of antipsychotic drugs is mediated by α1A-AR. Species:  Rat Tissue:  Mesenteric arteries. References:  92
Activation of sarcolemmal Na+-H+ exchanger. Species:  Rat Tissue:  Ventricular myocytes. References:  124
Silodosin (KM-3213: an α1A-AR selective antagonist) can improve the lower urinary tract symptoms associated with benign prostatic hyperplasia. Species:  Human Tissue:  Lower urinary tract. References:  114
Decreased α1A-AR mRNA in renal tissue during aging. Species:  Rat Tissue:  Kidney. References:  71
Contraction of right gastroepiploic artery. Species:  Human Tissue:  Artery. References:  47
Contractile responses in human subcutaneous arteries. Species:  Human Tissue:  Subcutaneous arteries. References:  59
Estrogen down-regulates α1A-AR expression in the urethral smooth muscle of female rats. Species:  Rat Tissue:  Intact urethra and isolated urethral smooth muscle cells. References:  12
Stimulation of myocyte hypertrophy. Species:  Rat Tissue:  Ventricular cardiomyocytes. References:  66
Inhibition of outward current via the acid-sensitive potassium channel TASK-1 by α1A-AR. Species:  Rat Tissue:  Heart. References:  103
Contraction of anal sphincter. Species:  Human Tissue:  Anal sphincter References:  95
Contraction of cauda epididymis. Species:  Rat Tissue:  Cauda epididymis References:  96
The involvement of urothelial α1A-AR in controlling the micturition reflex. Species:  Rat Tissue:  Bladder. References:  145
Interaction between H2S, NO and α1A-AR signalling in kidney of rats with left ventricular hypertrophy Species:  Rat Tissue:  Kidney References:  2-3
Activation of bladder mechanosensory A delta fibres. Species:  Rat Tissue:  Bladder References:  4
Role of α1A-AR in contraction of urethral smooth muscle in males and females. Species:  Mouse Tissue:  Urethra References:  6
Phasic responses of portal vein. Species:  Rat Tissue:  Portal vein References:  7
Effect of ageing and hypertension on desensitisation of vasoconstriction. Species:  Rat Tissue:  Aorta, tail and mesenteric arteries, responses and gene expression. References:  10
Trafficking of aquaporin-5 in salivary glands. Species:  Rat Tissue:  Salivary glands References:  14
Improved function and survival in heart failure. Species:  Mouse Tissue:  Ventricle References:  21-22
Inotropic response in the failing heart. Species:  Human Tissue:  Ventricular trabeculae References:  58
Role of α1A-AR in migration and gene expression in fibroblasts. Species:  Human Tissue:  Skin fibroblasts References:  73
Anti-apoptotic and protective effects in heart. Species:  Mouse Tissue:  Cardiomyocyte References:  120-121,140
Vascular tone. Species:  Mouse Tissue:  Femoral artery References:  149
Regulation and development of ovarian function. Species:  Rat Tissue:  Ovary- granulosa cells References:  146
Facilitates GABA release in the basolateral nucleus of the amygdala to mediate antiepileptic properties of norepinephrine. Species:  Rat Tissue:  Brain. References:  11
Trophic effect of norepinephrine on arterial intima-media and adventitia is augmented by injury and mediated by different α1-adrenoceptor subtypes. Species:  Rat Tissue:  Aorta. References:  150
Activation of α1A-AR promotes differentiation of rat-1 fibroblasts to a smooth muscle-like phenotype. Species:  Rat Tissue:  Transfected rat-1 fibroblasts. References:  109
α1A-AR inhibits PDGF receptor Tyr751 phosphorylation and PI3K activation. Species:  Human Tissue:  Transfected Rat-1 fibroblasts. References:  75
Altered adrenoceptor signaling following traumatic brain injury contributes to working memory dysfunction. Species:  Rat Tissue:  Brain (prefrontal cortex). References:  68
NOS inhibition by L-NNA abolishes cardioprotective effects of α1A-adrenoceptor. Species:  Rat Tissue:  Heart. References:  154

Physiological Consequences of Altering Gene Expression
Hypotension and a decreased pressor response to phenylephrine in α1A-AR knockout mice. Species:  Mouse Tissue:  In vivo. Technique:  Transgenesis. References:  107
α1A-AR regulates ERK survival pathway and decreases apoptosis in adult myocytes. Species:  Mouse Tissue:  Heart. Technique:  Gene knockouts. References:  53
Mice with systemic constitively active mutation (CAM) have increased adult neurogenesis and gliogenesis. Species:  Mouse Tissue:  Brain, adult neural stem cells. Technique:  Gene over-expression. References:  44
Mice with systemic constitively active mutation (CAM) of the α1A-AR are preconditioned against ischemia through PKC mechanism. Species:  Mouse Tissue:  Heart. Technique:  Gene over-expression. References:  108
Receptor over-expression inhibits Ins(1,4,5)P3 generation despite elevated PLC, measured as elevated p-MEK and p-ERK protein levels. Species:  Mouse Tissue:  Heart Technique:  Gene over-expression. References:  8
Cardioprotection in rats with α1A-adrenoceptor overexpression resembles that in non-transgenic littermates with preconditioning mediated by iNOS activation. Species:  Rat Tissue:  Heart. Technique:  Gene over-expression. References:  154
Cardiac specific overexpression of α1A-AR enhances cardiac contractility without hypertrophy. Species:  Mouse Tissue:  Heart. Technique:  Transgenesis. References:  74
Mice with systemic constitively active mutation (CAM) have increased synaptic plasticity, cognition and longevity. Species:  Mouse Tissue:  Brain. Technique:  Gene over-expression. References:  28
Mice with systemic constitively active mutation (CAM) of the α1A-AR have reduced incidence of cancer. Species:  Mouse Tissue:  In vivo. Technique:  Expression of CAM α1A-AR. References:  19
Skin fibroblast migration, TGFβ1, IGF-1, HA and PIP production in response to α1A-AR stimulation, are inhibited by treatment of α1A-AR siRNA Species:  Human Tissue:  Skin fibroblasts. Technique:  Gene knockdown with siRNA. References:  73
Increased post MI hypertrophy, ventricular dilatation, fibrosis, apoptosis and mortality in α1A-AR knockout mice. Species:  Mouse Tissue:  Heart. Technique:  Gene knockout. References:  146
Following coronary artery occlusion, rats with cardiomyocyte-specific α1A-AR over-expression display less fibrosis, hypertrophy and lung weight and show preserved LV ejection fraction compared to non-transgenic littermates Species:  Rat Tissue:  Heart. Technique:  Cardiomyocyte specific α1A-AR over-expression. References:  153
α1A-AR mediated inotrophy in failing RV myocardium requires the α1A-AR. Species:  Mouse Tissue:  Heart. Technique:  Gene knockout. References:  20
α1A-AR activation is anti-apoptotic and protective related to enhanced glucose uptake into the heart. Species:  Mouse Tissue:  Heart. Technique:  Gene over-expression. References:  120
α1A-AR activation promotes a favourable metabolic phenotype. Species:  Mouse Tissue:  Fat, skeletal muscle, heart, plasma. Technique:  Gene knockout and expression of CAM mutant. References:  121
Cardiac-specific over-expression of α1A-AR increases expression of relaxin receptor RXFP1. Species:  Mouse Tissue:  Heart. Technique:  Cardiomyocyte specific over expression of α1A-AR. References:  88
Down-regulation of α1A-AR attenuates ocular inflammation by inhibiting permeability of the blood brain barrier. Species:  Mouse Tissue:  Eye. Technique:  Exposure to light, blood flow, flow cytometry, PCR, immunohistochemistry. References:  125
Disruption of α1A/B-AR/CXCR4 heteromers inhibits α1A-AR function in vascular smooth muscle cells (human and rat). Species:  Human Tissue:  Vascular smooth muscle cells. Technique:  siRNA gene silencing, proximity ligation assay, Ca2+ influx, contraction. References:  131
α1A-AR counterbalance pathological pathways during post MI remodelling. Species:  Mouse Tissue:  Heart. Technique:  Gene knockout. References: